In this specification, a number of documents including patent applications and manufacturer's manuals is cited. The disclosure of these documents, while not considered relevant for the patentability of this invention, is herewith incorporated by reference in its entirety. More specifically, all referenced documents are incorporated by reference to the same extent as if each individual document was specifically and individually indicated to be incorporated by reference.
Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system (CNS) leading to disability in the majority of affected patients (1). The etiology of MS is unknown but epidemiological evidence suggests a complex interplay between genetic and environmental factors (2-4). An uncertain pathogenic mechanism, clinical heterogeneity and unpredictability of the outcome of individual patients add to the complexity of the disease (5).
The current working hypothesis for MS pathogenesis suggests that autoreactive T cells play a central role (6). However, histopathological studies have revealed a subset of MS patients exhibiting prominent deposition of immunoglobulins and complement activation in acute demyelinating lesions (7, 8). These patients respond particularly well to therapeutic plasma exchange (9). Moreover, B cell depletion by a therapeutic monoclonal antibody has a profound impact on inflammatory activity in MS (10). All these findings support the contention that at least in a subset of MS patients B cells and antibodies substantially contribute to the development and progression of the disease (11, 12). Despite this circumstantial evidence, a direct proof of clinically relevant antibodies in MS has not been established owing to the fact that specific molecular targets for humoral responses in MS remain undiscovered.
The technical problem can be seen in the provision of alternative or improved means and methods for diagnosing and/or treating multiple sclerosis.